The therapeutical use of polysulphated polysaccharides has been extensively studied over the past fifteen years. Upon sulphation of their hydroxyl groups, polysaccharides acquire particularly interesting biological activities.
Polysulphated cyclodextrins have been shown to reduce or to block the effects of teratogenic substances on foetal development (WO 91/16905), to improve tissue scar formation (WO 93/09790), to impair retroviral (HIV) replication (EP 447171) and to inhibit angiogenesis (WO 89/06536).
Polysulphated inulin has been shown to be an efficient inhibitor of the Complement system (U.S. Pat. No. 4,021,545; Immunol. 1965, 8:29; Pharmacology 1973, 9:74) and possesses anti-lipaemic properties (Arch. Int. Pharmacodyn. 1954, XCIX: 334.
Alginic acid sulphate has been shown to possess anticoagulant properties (U.S. Pat. Nos. 3,766,167 and 4,331,697) and has been proposed as an antithrombic resin composition in combination with synthetic resins (U.S. Pat. No. 4,822,615). Alginic acid sulphate was shown to inhibit retroviruses and was proposed as a substance to topically cleanse the human body (U.S. Pat. No. 5,100,879) and as a method of treatment of diseases (T-cell infections) caused by retroviruses (U.S. Pat. No. 4,840,941).
Sulphated pectinic acid has been used as non-absorbable synthetic sulphated polysaccharide to decrease cholesterol and fatty acid absorption (U.S. Pat. Nos. 5,616,570 and 5,063,210) and was found to inhibit pancreatic cholesterol esterase (U.S. Pat. No. 5,484,777).
Polysulphated glycosaminoglycans such as chondroitin polysulphate have been found to stimulate the production of extracellular matrix macromolecules (hyaluronan, chondroitin sulphate proteoglycan) by connective tissue cells (synovial cells, fibroblasts, articular cartilage cells) (Acta Rheumatol. 1977, 1:75; J. Rheumatol. 1979, 6:554; J. Rheumatol. 1999, 26:1663).
Chondrocytes are incapable of repairing endochondral lesions of articular cartilage and these lesions inevitably lead to the development of osteoarthritis. Attempts at repairing enchondral lesions of articular cartilage by implantation of human autologous chondrocytes have been proposed with limited success (N. Engl. J. Med. 1994, 331:889). It has been demonstrated that implantation of human chondrocytes in biocompatible and biodegradable hydrogel grafts improves the possibilities to restore these articular cartilage lesions (PNAS 2002, 99:9996-10001;. Ann NY Acad Sci, 2002, 961:118-122).
The technique of chondrocyte culture in alginate beads glued together with fibrin gel has been described recently (Ann. Rheum. Dis. 2001, 60 781-790). In this culture condition, chondrocytes colonize the whole alginate/fibrin hydrogel and form a hyaline-like cartilagineous tissue.